Using a microfluid mixer

ABSTRACT

A method includes directing first and second fluids into a plurality of first ports fluidly connected to a mixing chamber disposed between a first plate and a base plate, guiding the first and second fluids into a mixing chamber, directing the first and second fluid into a plurality of second ports fluidly connected to the plurality of first ports, guiding the first and second fluids from the plurality of second ports into another mixing chamber disposed between a second plate and the first plate and fluidly connected to the mixing chamber, activating a heating element to heat one of the first and second fluids entering the mixing chamber, creating a temperature gradient between the first and second fluids entering the mixing chamber, and operating a diaphragm operatively associated with the mixing chamber and the another mixing chamber to agitate the first and second fluids to form a fluid mixture.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No. 11/834,973filed Aug. 7, 2007, the disclosure of which is incorporated by referenceherein in its entirety.

BACKGROUND

When fluids are present in microliter quantities, it is generallydesirable to mix them in channels or passages having micrometer-sizeddimensions so that the fluids are not wasted. However, fluids generallybehave differently when they have to pass through channels and passageshaving micrometer-sized dimensions. For example, water flowing through achannel having a diameter equal to the width of a human hair behaveslike honey. Even under pressure, the water travels less than onecentimeter per second. Mixing of two different fluids in channels orpassages that have micrometer-sized dimensions is therefore difficultbecause at such dimensions, the fluid's ability to flow in a turbulentmanner is minimized. In channels or passages having micrometer-sizeddimensions, static diffusion between two different fluids takes aprohibitively long time.

It is therefore desirable to have a mixer that can facilitate the mixingof a plurality of different fluids when the fluids are present inquantities on the order of microliters.

SUMMARY

Disclosed herein is a method including directing a first fluid and asecond fluid into a plurality of first ports fluidly connected to amixing chamber disposed between a first plate and a base plate, guidingthe first and second fluids into a mixing chamber, directing the firstand second fluid into a plurality of second ports fluidly connected tothe plurality of first ports, guiding the first and second fluids fromthe plurality of second ports into another mixing chamber disposedbetween a second plate and the first plate and fluidly connected to themixing chamber, activating a heating element to heat one of the firstand second fluids entering the mixing chamber, creating a temperaturegradient between the first and second fluids entering the mixingchamber, and operating a diaphragm operatively associated with themixing chamber and the another mixing chamber to agitate the first fluidand the second fluid to form an intimate fluid mixture.

Also disclosed is a method of manufacturing a mixer. The method includespouring a ceramic precursor into a first mold, a second mold and a thirdmold. The first mold has a shape of a trough or a base plate, the secondmold has a shape of a top plate, the third mold has a shape of a firstplate. The method further includes gelling the ceramic precursors in thefirst mold, the second mold and the third mold to form a green baseplate, a green top plate and a green first plate, and removing the greenbase plate, the green top plate and the green first plate from therespective molds. The method still further includes co-firing the greenbase plate, the green top plate, and the green first plate to form aceramic base plate, a ceramic top plate and a ceramic first plate. Theceramic first plate includes a plurality of ports for an entry of afirst fluid and a second fluid, a mixing chamber fluidly connected withthe plurality of ports, and a heating element. The ceramic base plate isinterlocked with the ceramic top plate and the ceramic first plate, anda diaphragm is disposed upon one of the first plate and the top plate.

BRIEF DESCRIPTION OF FIGURES

FIG. 1 is an exemplary depiction of one embodiment of the mixer;

FIG. 2 is an exemplary depiction of one embodiment of a first plate;

FIG. 3 is an exemplary depiction of the units of different fluids whenthey first encounter each other in the mixing chamber and theirsubsequent conversion into an intimately mixed fluid mixture;

FIG. 4A depicts an exemplary embodiment of the top plate that can beused to assemble the mixer;

FIG. 4B depicts an exemplary embodiment of the middle plate that can beused to assemble the mixer;

FIG. 4C depicts an exemplary embodiment of the bottom plate that can beused to assemble the mixer;

FIG. 5A depicts one variation representing a mixer that can be obtainedby assembling the plates that are shown in the FIGS. 4A, 4B and 4C;

FIG. 5B depicts another variation representing a mixer that can beobtained by assembling the plates that are shown in the FIGS. 4A, 4B and4C;

FIG. 6A depicts one exemplary embodiment of the respective plates thatcan be used to assemble the mixer;

FIG. 6B depicts one exemplary embodiment of the mixer formed byassembling the plates depicted in the FIG. 6A;

FIG. 6C depicts another exemplary embodiment of the mixer formed byassembling the plates depicted in the FIG. 6A;

FIG. 7 depicts a plurality of mixers that can be used to perform avariety of functions on fluids that are available in small quantities;the mixers can be arranged to be in series, parallel or in a combinationor series and parallel.

DETAILED DESCRIPTION

Disclosed herein is a mixer that advantageously uses a combination ofphysical agitation and temperature gradients to facilitate the mixing ofa plurality of fluids, when the fluids are present in small quantitieson the order of microliters. In one embodiment, the mixer employstemperature gradients in a plurality of directions to facilitatediffusion between the plurality of fluids while at the same timeemploying physical agitation to increase turbulence between the fluids.In an exemplary embodiment, the mixer is manufactured from a ceramicmaterial, which enables metal containing components of the mixer, suchas the heating elements to be co-fired along with the ceramic materialthus minimizing the manufacturing and assembly time.

With reference to the exemplary embodiments depicted in FIGS. 1 and 2,the mixer 100 comprises a trough 102 that comprises within it a plate112, or a plurality of plates 112, 114, and 116. The trough 102 has afirst surface 103 upon which the plate or the plurality of plates aredisposed and a second surface 104 that is in thermal communication witha heating element. The first surface 103 and the second surface 104 areopposedly disposed. Each plate comprises a mixing chamber 148, a firstchannel 130 in fluid communication with a first port, a first heatingelement 118 and an optional first exit channel 142. The first heatingelement 118 generally produces temperature gradients in a firstdirection. The mixer 100 further comprises a diaphragm 146 that can beused for physical agitation of the fluids contained in the mixingchamber 148. The mixer 100 additionally comprises a second globalheating element 144 that can be used to produce gradients in a seconddirection to further facilitate diffusion of the fluids contained in themixer.

As can be seen in FIGS. 1 and 2, the mixer 100 comprises a plurality ofplates 112, 114 and 116, and so on. Each plate can comprise a singlechannel or a plurality of channels 130, 131, 132 and 133 for permittingthe respective fluids to enter the mixing chamber 148. Each channel isin fluid communication with a respective port 130′, 131′, 132′ and 133′respectively. The mixing chamber 148 permits the respective fluids toundergo agitation by virtue of the diaphragm 146 and diffusion by virtueof the temperature gradients established by the use of the heatingelements 118, 119, 120 and 121, depicted in FIG. 2.

While the plate 112 depicted in FIG. 2 has a rectangular cross-section,it is to be noted that the cross-section may have any desired geometry,such as, for example, square, circular, triangular or polygonal.

With reference now to FIG. 2, the first channel 130 and the secondchannel 131 are disposed on one side of the plate 112, while the thirdchannel 132 and the fourth channel 133 are disposed on an opposing sideof the plate 112. In one embodiment, the channels extend radiallyoutwards from the mixing chamber 148 to the vertical edges of the plate112 and permits the first fluid present in the first chamber 150 and thesecond fluid present in the second chamber 152 to travel into the mixingchamber 148. Additional channels such as a fifth, a sixth, a seventh, aneighth channel (not shown), and so on, may be introduced into the plate112 for purposes of introducing a third fluid, a fourth fluid, and soon, into the mixing chamber 148. As will be detailed later in FIGS. 4A,4B, 4C, 5A and 5B, the channels do not always extend out to the verticaledges of the plate, but can have ports disposed upon a horizontalsurface of the plate.

Each plate can also comprise a single heating element or a plurality ofheating elements for facilitating agitation of the fluid in the mixingchamber 148. Alternatively, the heating elements may be disposed incavities situated between the plates if desired. In one embodiment, theheating elements can be resistance heaters and are in electricalcommunication with a source of electricity (not shown).

As can be seen in FIG. 2, the plate 112 may comprise a first heatingelement 118, a second heating element 119, a third heating element 120and a fourth heating element 121, each heating element being radiallydisposed about the mixing chamber 148. The heating elements may bepresent in a single horizontal plane in the respective plates oralternatively each heating element can be at a different elevationwithin the plate. FIG. 1 depicts one embodiment, wherein the firstheating element 118 is disposed along a first surface of the plate 112,while the third heating element is disposed along the second surface ofthe plate 112. The first surface and the second surface of the plate 112are opposed to each other.

The heating elements 118, 119, 120 and 121 are held at differenttemperatures in order to create a temperature gradient within the mixingchamber 148 that facilitates the diffusion of the fluids into oneanother. When the mixer is placed on its second surface 104, the firstelements can be used to create a first direction. In one embodiment, thefirst direction is a vertical direction. For example in FIG. 2, whilethe first heating element 118 is held at a temperature of 50° C., thesecond heating element 119 can be held at a temperature of 60° C., whilethe third heating element 120 can be held at a temperature of 70° C.,and the fourth heating element 121 can be held at a temperature of 80°C. When a plurality of plates are disposed upon one another as depictedin FIG. 1, the temperature gradient can be extended to exist through theplurality of heating elements present in the plurality of plates. Forexample with reference to the FIG. 1, while the heating elements presentin the first plate 112 are operated at temperatures of about 50 to about60° C., those present in the second plate 114 can be operated attemperatures of about 60 to about 70° C., while those present in thethird plate 116 can be operated at temperatures of about 70 to about 80°C., and so on.

In one embodiment, the heating element may be a metallic resistive coilthat heats up upon passing an electric current through the coil. Inanother embodiment, the heating element can comprise an electricallyconducting ceramic, metallic and/or a carbonaceous material that heatsup upon passing an electric current through the conducting ceramicand/or a carbonaceous material.

Suitable materials for fabrication of the heating element includesilicon carbide, molybdenum disilicide, tungsten disilicide, lanthanumchromate, zirconium diboride, titanium nitride, titanium diboride, tinoxide, copper oxide, copper, nickel, gold, silver, conductive carbonfibers, conductive carbon blacks, carbon nanotubes, or the like, or acombination comprising at least one of the foregoing materials.

The dimensions of the heating element will depend on its composition andmethod of fabrication. The heating element may be disposed upon thetrough or the plurality of plates by spray coating, spin coating, or thelike. When the heating element is coated onto the plates, it generallyhas a width of about 0.001 to about 0.005 millimeters, specificallyabout 0.002 to about 0.004 millimeters, and more specifically about0.003 millimeters. The thickness of the heating element is about 0.0005to about 0.04 millimeters, specifically about 0.001 to about 0.03millimeters, and more specifically about 0.005 to about 0.02millimeters. A preferred thickness is about 0.01 millimeter. The lengthof the heating element may be proportional to the number of platesincluded in the mixer 100.

Each plate may be provided with a plurality of ports through which themixed fluid can be removed. If each plate is provided with a port, thenit is desirable for these ports to be in fluid communication with oneanother so that the mixed fluid can be removed from the mixer. In oneembodiment, it is desirable for only the uppermost plate (e.g., thethird plate 116 in FIG. 1) to have an exit channel 142 that is in fluidcommunication with the mixing chamber 148 through which the mixed fluidcan be extracted. In one embodiment, the port 142 can be in fluidcommunication with a pump (not shown). The pump can be controlled by acontrolling device such as a computer and can be used to periodicallyextract mixed fluid from the mixer 100.

Each plate is also provided with an interlocking mechanism (i.e., alocking and unlocking mechanism) (not shown) by which it can be fixedlyattached to the plate disposed above it as well as the plate disposedbelow it during operation. The first plate 112 that is in communicationwith the trough 102 has an interlocking mechanism by which it can befixedly attached to the trough 102. Examples of such interlockingmechanisms include threads, screws, bolts, dowels, adhesive, mortise andtenon joints, dovetail joints, lap joints, tongue and groove joint, orthe like, or a combination comprising at least one of the foregoingjoints.

In one embodiment, the respective plates and/or the trough in theirrespective green forms (prior to sintering) are assembled and thenco-sintered to form the mixer 100 or a part of the mixer. During thesintering process, the respective plates and/or the trough react witheach other and are permanently locked into position.

Each plate may also be provided with a socket and a plug so that theheating elements in the respective plates can be in electricalcommunication with one another. It is desirable for the plate disposedupon and in intimate contact with the first surface 103 of the trough102 (e.g., the first plate 112 in the FIG. 1) to be in electricalcommunication with a source of electrical energy.

While the mixer 100 in FIG. 1 is depicted as having 3 plates, it may bedesirable to have as many plates as possible. The use of a larger numberof plates permits the respective fluids to be mixed as distributedmicrounits as depicted in FIG. 3. FIG. 3 depicts an idealized view ofthe respective fluid phases in the mixing chamber prior to and afterundergoing agitation.

The respective plates have a length of about 20 to about 70 millimeters,specifically about 30 to about 50 millimeters, and more specificallyabout 35 to about 45 millimeters. A preferred length is about 40millimeters. The respective plates have a width of about 10 to about 50millimeters, specifically about 20 to about 40 millimeters, and morespecifically about 25 to about 35 millimeters. A preferred width isabout 30 millimeters.

Each plate prior to sintering has a thickness of about 0.05 to about 0.5millimeters, specifically about 0.08 to about 0.2 millimeters. Apreferred plate thickness prior to sintering is about 0.1 millimeters.The channels and ports generally have diameters of about 1 to about 3millimeters, specifically about 1.3 to about 2.7 millimeters, and morespecifically about 1.6 to about 2.3 millimeters. A preferred diameterfor the channel and the ports is about 2 millimeters.

The mixing chamber generally has a diameter of about 5 to about 15millimeters, specifically about 6 to about 13 millimeters, and morespecifically about 7 to about 12 millimeters. An exemplary diameter forthe mixing chamber is about 10 millimeters. It is to be noted that theaforementioned dimensions can be varied depending upon thecharacteristics and the amount of the fluids.

The plates and the trough can be manufactured from a metal, a ceramic,an organic polymer, or a combination comprising at least one of theforegoing materials. It is generally desirable for the plates and thetrough to be manufactured from a ceramic material. Examples of suitableceramic materials are silica, alumina, titania, ceria, zirconia, aluminawith silica additives, glass ceramic, borosilicate glass, aluminumnitride, cordierite based glass (Al₂O₃/MgO/SiO₂), or the like, or acombination comprising at least one of the foregoing ceramic materials.

The use of a ceramic material has a number of advantages. The heatingelements can be incorporated into the green ceramic material (prior toits firing) and the combination of the ceramic plate or trough with theincorporated heating element can be subjected to firing. This reducesthe number of steps used to manufacture the mixer thereby reducing thenumber of production steps and the cost of production.

The uppermost plate (e.g., plate 116 in FIG. 1) has disposed upon itsupper surface a diaphragm 146 that serves to agitate the respectivefluids and to bring the molecules of the fluid into intimate contactwith each other. The diaphragm 146 can be manufactured from a ductilemetal, a metal alloy, or an organic polymer. Examples of suitable metalsare aluminum, stainless steel, copper, brass, or the like.

It is desirable for the diaphragm 146 to comprise an organic polymer.The organic polymer can comprise a wide variety of thermoplastic resins,blend of thermoplastic resins, thermosetting resins, or blends ofthermoplastic resins with thermosetting resins. The organic polymer mayalso be a blend of polymers, copolymers, terpolymers, or combinationscomprising at least one of the foregoing organic polymers. The organicpolymer can also be an oligomer, a homopolymer, a copolymer, a blockcopolymer, an alternating block copolymer, a random polymer, a randomcopolymer, a random block copolymer, a graft copolymer, a star blockcopolymer, a dendrimer, or the like, or a combination comprising atleast one of the foregoing organic polymers. Exemplary organic polymersfor use in the diaphragm 146 are elastomers that have glass transitiontemperatures below room temperature.

Examples of the organic polymer are polyacetals, polyolefins,polyacrylics, polycarbonates, polystyrenes, polyesters, polyamides,polyamideimides, polyarylates, polyarylsulfones, polyethersulfones,polyphenylene sulfides, polyvinyl chlorides, polysulfones, polyimides,polyetherimides, polytetrafluoroethylenes, polyetherketones, polyetheretherketones, polyether ketone ketones, polybenzoxazoles,polyphthalides, polyacetals, polyanhydrides, polyvinyl ethers, polyvinylthioethers, polyvinyl alcohols, polyvinyl ketones, polyvinyl halides,polyvinyl nitriles, polyvinyl esters, polysulfonates, polysulfides,polythioesters, polysulfones, polysulfonamides, polyureas,polyphosphazenes, polysilazanes, styrene acrylonitrile,acrylonitrile-butadiene-styrene (ABS), polyethylene terephthalate,polybutylene terephthalate, polyurethane, ethylene propylene dienerubber (EPR), polytetrafluoroethylene, fluorinated ethylene propylene,perfluoroalkoxyethylene, polychlorotrifluoroethylene, polyvinylidenefluoride, or the like, or a combination comprising at least one of theforegoing organic polymers.

Examples of blends of thermoplastic resins includeacrylonitrile-butadiene-styrene/nylon,polycarbonate/acrylonitrile-butadiene-styrene, acrylonitrile butadienestyrene/polyvinyl chloride, polyphenylene ether/polystyrene,polyphenylene ether/nylon, polysulfone/acrylonitrile-butadiene-styrene,polycarbonate/thermoplastic urethane, polycarbonate/polyethyleneterephthalate, polycarbonate/polybutylene terephthalate, thermoplasticelastomer alloys, nylon/elastomers, polyester/elastomers, polyethyleneterephthalate/polybutylene terephthalate, acetal/elastomer,styrene-maleicanhydride/acrylonitrile-butadiene-styrene, polyetheretherketone/polyethersulfone, polyether etherketone/polyetherimidepolyethylene/nylon, polyethylene/polyacetal, or the like.

Examples of thermosetting resins include polyurethane, natural rubber,synthetic rubber, epoxy, phenolic, polyesters, polyamides,polysiloxanes, or the like, or a combination comprising at least one ofthe foregoing thermosetting resins. Blends of thermoset resins as wellas blends of thermoplastic resins with thermosets can be utilized. Anexemplary thermosetting resin is polydimethylsiloxane (PDMS). It is tobe noted that the diaphragm may be substituted by a piston or anothersuitable reciprocatory device.

The diaphragm 146 is in physical communication with a source ofvibration (not shown). An example of a source of vibration is areciprocatory device such as a piston connected to a crank shaft that isin slideable communication with the mixing chamber. In one embodiment,the source of vibration is manual. In another embodiment, the source ofvibration can be mechanical or electromechanical. Examples of mechanicalor electromechanical sources of vibration are pumps, piezoelectricdrives, shape memory alloy drives, pneumatic drives, or the like. Thesource of vibration causes the diaphragm to oscillate promoting anagitation of the respective fluids. In an exemplary embodiment, thediaphragm oscillates in the vertical direction. The source of vibrationcan also be used to displace mixed fluid from the mixing chamber 148 forextraction through the first exit channel 142.

As noted above, a second heating element 144 is disposed at the secondsurface 104 located at the bottom of the trough. The second heatingelement 144 can be used to heat any portion of the trough and therebycreate a second temperature gradient. As depicted in the FIG. 1, it isused to create a temperature gradient in the horizontal direction. It ispreferably used to heat one of the fluids introduced into the mixer sothat the difference in temperature between the fluids in the mixingchamber 148 will facilitate diffusion of the fluids into each other.

FIGS. 4A, 4B 4C, 5A and 5B depict exemplary variations of the embodimentdepicted in FIG. 1. In the embodiment depicted in FIGS. 4A, 4B 4C, 5Aand 5B, the mixer 200 (FIGS. 5A and 5B) comprises a base plate 202 (FIG.4C), a middle plate 204 (FIG. 4B) and a top plate 206 (FIG. 4A). FIGS.5A and 5B depict the assembly of the parts shown in FIGS. 4A, 4B and 4C.As can be seen in FIGS. 5A and 5B, the top plate 206 is disposed and inintimate contact with a middle plate 204 which is disposed upon and inintimate contact with the base plate 202, the respective intimatecontacts preventing the loss of fluids due to leakage.

With reference now to FIGS. 4A, 4B 4C, 5A and 5B, the top plate and themiddle plate each comprise a first port 210 and a second port 220 intowhich the first fluid and the second fluid are introduced respectively.The respective fluids travel to the mixing chamber 248 via the firstchannel 212 and the second channel 222 respectively. Upon being mixed inthe mixing chamber 248, the mixed fluid can be extracted from the mixer200 via the third port 230 and the third channel 232. The mixed fluidcan be extracted from the mixer via an exit channel and port (notshown).

FIGS. 6A, 6B and 6C depict another exemplary variation of the embodimentdepicted in FIG. 1. In this embodiment, the mixer 300 comprises 4 ormore plates 302, 312, 322 and 332. Each plate comprises a first port304, a second port 306, channel 308 and a mixing chamber 310. The firstfluid is introduced into the first port 304, while the second fluid isintroduced into the second port 306. As can be seen in the assembledmixers 300 in FIGS. 6B and 6C, the respective channels 308 are arrangedin alternating plates so as to enable a staggered entry of therespective fluids into the mixing chamber. This facilitates theagitation of the first fluid and the second fluid. The mixed fluid canbe extracted via an exit channel (not shown).

In another embodiment depicted in FIGS. 6B and 6C, the alternatingplates can have different diameters for the respective mixing chamber.In other words, the mixing chamber has different dimensions along itsheight. This causes the mixing chamber to have an irregular shape andpermits the respective fluids to be introduced into the mixing chamberat different locations, thus facilitating further agitation of the firstfluid and the second fluid.

With reference once again to FIGS. 1, 4A, 4B, 4C, 5A, 5B, 6A, 6B and 6C,in one embodiment, in one manner of using the mixing device 100, a firstfluid is disposed in the first chamber 150 while a second fluid isdisposed in the second chamber 152. Capillary action can draw therespective fluids into the channels 130, 132, 134, 136, 138 and 140.Additionally, pressure can be used to force the respective fluids intothe mixing chamber 148. Once the fluids are disposed into the respectivefirst and second chambers, the second heating element can be activatedthus creating a temperature gradient in the horizontal direction. As thefluid enters the mixing chamber, the diaphragm 148 and the first heatingelements can be activated, thus promoting agitation and diffusion of thefluids present in the mixing chamber. The mixed fluids can be extractedfrom the first exit channel 142.

As noted above, the respective fluids can be heated during the mixing.In an exemplary embodiment, the fluids are generally heated to atemperature of about ±15° C., specifically about ±10° C., and morespecifically about ±5° C. of the dewpoint.

The mixer can be manufactured in a variety of different ways. In oneadvantageous method of manufacturing the mixer, the various componentsthat comprise ceramics can be co-fired with the metal parts that areused for the heating elements. In another embodiment, the heatingelements comprise ceramic materials that can be co-fired with theceramic material used in the trough, the base plate or the plurality ofplates.

In one embodiment, in one method of manufacturing the mixer, the methodcomprises pouring a ceramic precursor into a first mold, a second mold,a third mold, and so on; the first mold having a shape of the trough orthe base plate; the second mold having a shape of the top plate; and thethird mold having a shape of the first plate. If desired, the firstmold, the second mold and the third mold each have a cavity or aplurality of cavities for incorporating the first heating element andthe second heating element. The ceramic precursors are then subjected togelling within the respective molds to form green parts (e.g., a greenbase plate, a green top plate and a green first plate). The green partsare then removed from the respective molds. They may optionally besubjected to a vacuum to remove any solvents and unreacted reactants. Anoptional heating element may be disposed in the respective cavities ifdesired. As noted above, the heating element may be ceramic or metallic.Metallic heating elements are disposed in the cavity, while ceramicheating elements may be sprayed or coated onto the respective greenparts.

The respective green parts with the corresponding heating elements arethen co-fired to produce ceramic parts (e.g., a ceramic base plate, aceramic top plate and a ceramic first plate). The ceramic parts are thenassembled into the mixer by virtue of the interlocking devices provided.A diaphragm is then disposed on top of the top plate for effectiveagitation of the fluids. The diaphragm is generally bonded to the topplate using an adhesive. Appropriate adhesives such as cyano-acrylateesters or epoxies can be used for the bonding.

In one embodiment, the respective green parts can be first gelled inrespective molds and then fired (also referred to as sintering). Inanother embodiment, the various respective parts such as the plates andtrough can be co-sintered to form a single unit.

In one embodiment, the respective plates and/or the trough in theirrespective green forms (prior to sintering) are assembled and thenco-sintered to form a mixer 100 that comprises a single piece. Duringthe sintering process, the respective plates and/or the trough reactwith each other and are permanently locked into position. In analternative embodiment, only selected plates can be co-sintered togetherand then assembled to form the mixer 100. The sintered mixer can then besubjected to machining, finishing and assembly operations to form themixer 100.

The finishing operations can include machining for providing therespective plates with the ports and the channels as well as forremoving rough edges and the like. In one embodiment, the ports and thechannels can be machined by using electrodischarge machining, ultrasonicmachining, micro-ultrasonic machining, abrasive flow machining,electrochemical machining, micro-electrochemical machining, water jetmachining, or the like, or a combination comprising at least one of theforegoing processes. The machining of the ports and channels can be doneprior to or after sintering.

The finished plates may be coated with various surface finishes that canpromote a change in the nature of the surfaces from wetting tonon-wetting surfaces. For example, a sintered plate can have a surfacecoated with polytetrafluoroethylene or polydimethylsiloxane to improvethe non-stick properties of the surface. Alternatively, the surface maybe coated with a layer of silane coupling agent to reduce the non-stickproperties of the surface (e.g., to facilitate a greater residence timeof the molecules on the surface).

In one embodiment, a plurality of mixers 100 can be connected in amodular fashion to facilitate a plurality of operations. With referencenow to FIG. 7, a plurality of mixers 100, 300, 500 and 700 can bearranged in series, parallel or a combination of series and parallel fora microfluidic mixing device. For example, in FIG. 7, the mixer 100 canbe used to mix a first fluid with a second fluid to produce a firstmixed fluid, the mixer 300 can be used to wash the first mixed fluid,the mixer 500 can be used to mix a third fluid with a fourth fluid toproduce a second mixed fluid, while the mixer 700 can be used to mix thefirst mixed fluid with the second mixed fluid to produce a third mixedfluid. In this manner, a plurality of mixers can be used to facilitatemixing, reacting, separating, washing, and the like of a combination ofdifferent fluids each of which are available in microliter quantities.The mixing, reacting, separating, washing, and the like, can beconducted at a variety of different physical conditions involvingdifferent pressure regimes, temperature regimes, and the like.

The mixer has a number of advantages over other conventional mixers. Itcan be advantageously used to blend small quantities of fluid withoutany loss of the fluid. It can also be advantageously used forcombinatorial chemistry or laboratory on chip experiments, where smallquantities of the respective fluids are dispensed, mixed, reacted andanalyzed. The use of a ceramic material facilitates the manufacture ofthe plate and the trough in a single operation. It also permits theplates and trough to be manufactured in single pieces that can bequickly assembled by using the aforementioned interlocking mechanisms.Since the mixers can be connected with each other in a modular fashion,they can be quickly and easily connected and disconnected depending uponthe number of operations to be performed on the respective fluids.

While the invention has been described with reference to exemplaryembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particular situationor material to the teachings of the invention without departing from theessential scope thereof. Therefore, it is intended that the inventionnot be limited to the particular embodiment disclosed as the best modecontemplated for carrying out this invention, but that the inventionwill include all embodiments falling within the scope of the appendedclaims.

1. A method comprising: directing a first fluid and a second fluid intoa plurality of first ports fluidly connected to a mixing chamberdisposed between a first plate and a base plate; guiding the first andsecond fluids into a mixing chamber; directing the first and secondfluid into a plurality of second ports fluidly connected to theplurality of first ports; guiding the first and second fluids from theplurality of second ports into another mixing chamber disposed between asecond plate and the first plate and fluidly connected to the mixingchamber; activating a heating element to heat one of the first andsecond fluids entering the mixing chamber; creating a temperaturegradient between the first and second fluids entering the mixingchamber; and operating a diaphragm operatively associated with themixing chamber and the another mixing chamber to agitate the first fluidand the second fluid to form an intimate fluid mixture.
 2. The method ofclaim 1, further comprising extracting the intimate fluid mixture froman extraction port in the first plate.
 3. The method of claim 1, furthercomprising activating another heating element to heat one of the firstand second fluids entering the another mixing chamber.
 4. The method ofclaim 3, creating another temperature gradient between the first andsecond fluids entering the another mixing chamber.
 5. The method ofclaim 4, wherein creating the another temperature gradient includesactivating the another heating element such that the another temperaturegradient is distinct from the temperature gradient.
 6. The method ofclaim 1, further comprising: directing a third fluid and a fourth fluidinto a plurality of third ports fluidly connected to yet another mixingchamber disposed between a third plate and the second plate, the yetanother mixing chamber being fluidly connected to the mixing chamber andthe another mixing chamber.
 7. The method of claim 6, furthercomprising: guiding the first and second fluids into a mixing chamber;and agitating the first, second, third and fourth fluids throughoperation of the diaphragm to form an intimate fluid mixture.
 8. Themethod of claim 6, wherein directing the third fluid and the fourthfluid into a plurality of third ports includes guiding third and fourthfluids that are distinct from the first and second fluids into theplurality of third ports.
 9. A method of manufacturing a mixercomprising: pouring a ceramic precursor into a first mold, a secondmold, and a third mold, the first mold having a shape a base plate; thesecond mold having a shape of a top plate; the third mold having a shapeof a first plate; gelling the ceramic precursors in the first mold, thesecond mold and the third mold to form a green base plate; a green topplate and a green first plate; removing the green base plate, the greentop plate and the green first plate from the respective molds; co-firingthe green base plate, the green top plate and the green first plate withthe optional heating elements to form a ceramic base plate, a ceramictop plate and a ceramic first plate, the ceramic first plate including aplurality of ports for an entry of a first fluid and a second fluid, amixing chamber fluidly connected with the plurality of ports;interlocking the ceramic base plate with the ceramic top plate and/orthe ceramic first plate; and disposing a diaphragm upon one of the firstplate and the top plate.
 10. The method of claim 9, wherein theinterlocking the ceramic base plate with the ceramic top plate theceramic first plate comprises co-sintering the ceramic base plate withthe ceramic top plate and the ceramic first plate.
 11. The method ofclaim 9, further comprising: forming at least one heating element cavityin the third mold.
 12. The method claim 11, further comprising: mountinga heating element in the at least one heating element cavity.